Dibromo-j-(dihydrocarbyloxy-
phosphinyloxy)butyratex



United States Patent 3,278,648 2,3-DIBROMO-3-(DIHYDROCARBYLOXY- PHOSPHINYLOXY)BUTYRATES Mason M. Turner and Milton Silverman, Modesto, Calif, assignors to Shell Oil Company, New York, N.Y., a corporation of Delaware No Drawing. Original application May 23, 1960, Ser. No. 30,776, now Patent No. 3,081,220, dated Mar. 12, 1963. Divided and this application Mar. 7, 1963, Ser. No.

5 Claims. or. 260-941) This application is a division of application Serial No. 30,776, filed May 23, 1960, now US Patent No. 3,081,- 220, granted March 12, 1963.

This invention relates to novel compounds useful for the destruction of noxious fungi. More particularly, this invention is the discovery that certain neutral esters of 3-phospho-oxy-2,3-dibromo-substituted propionic acids are excellent fungicides. These compounds are particularly effective against soil-borne fungi.

In these fungicides, the essential structural features which impart the fungicidal activity are represented by the formula:

That is to say, these compounds contain the structure of propionic acid substituted on the number three carbon atom by a phospho-oxy group, and on that carbon atom, and on the immediately adjacent carbon atom in the number two position, by bromine atoms.

These fungicides are most conveniently prepared by bromination of the corresponding esters of 3-phospho-oxysubstituted 2-propenoic acids. These esters are a widely known, well established class. All are known to be insecticidally active. However, the art does not show them to be fungicidally active as well, and it has been found that they in fact exhibit little if any fungicidal activity. The brominated derivatives of such acids, however, have been found to be highly active fungicides.

Described in more detail, the fungicides provided by this invention have the general formula:

Br Br wherein each R is hydrocarbon of the group consisting of alkyl, aryl and aralkyl groups, R is hydrogen or alkyl, R is hydrogen, halogen or alkyl, each of these alkyl, aryl or aralkyl groups containing, for example, up to carbon atoms; and R is aryl or aralkyl of up to 10 carbon atoms.

In these fungicides, the alkyl groups represented by R, R R and R may be either straight chain or branched chain in configuration.

Illustrative examples of the groups represented by R, R R and R include the methyl, ethyl, nand isopropyl groups; the various isomeric butyl, pentyl, hexyl, octyl and nonyl groups; the phenyl group; the naphthyl group; the benzyl, phenethyl, p-methylbenzyl and like aralkyl groups; the isomeric tolyl groups; the isomeric xylyl groups; the ethylphenyl groups; the 2,4- and 3,5-dimethylphenyl groups and like alkaryl groups, and the like.

Of particular interest because of their high fungicidal activity are the compounds of the formula wherein R is each lower molecular weight alkyl of up to seven carbon atoms, R is aryl up to ten carbon atoms, or aralkyl up to ten carbon atoms, particularly the phenyl group or the benzyl group; R is hydrogen, or halogen or alkyl of up to seven carbon atoms. The highest fungicidal activity is shown by the phosphates of this class wherein R, and R is each alkyl of up to four carbon atoms, and R is hydrogen. These particular fungicides have the formula O R R 0 Ro -f'-ot =hi-o-R A wherein the various symbols have the respective meanings already set out.

This class of compounds is well known in the art, being described in British Patent No. 783,697.

Bromination of these esters is generally most effectively accomplished by contacting the ester with free bromine, a suitable solvent being used if necessary to moderate the reaction. The addition of the bromine should be conducted at a rather low temperature to avoid decomposition of the phosphorus-containing reactant and/or the phosphorus-containing product. Thus, during addition of the bromine, the reaction mixture temperature should be kept below about 40 C. After addition of the bromine is complete, the reaction mixture may be warmed to a somewhat higher temperature-preferably not exceeding about 60 C.-to insure completion of the bromination. In many cases, it may be found best to maintain the reaction at a low temperature-say, in the range of from about -5 C. to about 30 C.-during addition of the bromine, then warm the mixture to a higher temperature to insure complete reaction. A particularly suitable solvent in most cases is methylene dichloride. Actinic radiation, for example, ultraviolet light, may be used to promote the addition of the bromine.

The product is generally most easily worked up by distillation techniques. In many cases, it will be found that little or no side reactions occur, so that a sufficiently pure product will be obtained by simply stripping the solvent from the final reaction mixture, preferably using sub-atmospheric pressure as necessary to avoid thermal decomposition of the product. If a pure product is required, it can be obtained by extraction, distillation or other known means for purifying organo-phosphorus compounds.

Since the bromide reacts substantially only with the olefinic double bond of the ester reactant, in many cases, to obtain a pure product it is necessary only to add the stoichiometric amount of bromine. Alternatively, the course of the reaction may be checked, by means of infrared spectrum analysis for example, to determine when all of the olefinic double bonds of the ester reactant have been reacted with bromine.

Should some of the ester reactant remain in the final mixture, it may be allowed to remain therein, since it will not affect the fungicidal activity of the brominated product, but will be present merely as an inert diluent. Of course, where the ester reactant is a good insecticide, some of it may be allowed in the product to provide that prodnet with additional insecticidal activity.

This method for bromination of the esters is demonstrated by the following particular instances of its application.

(1) 43 grams of dimethyl 1-carbomethoxy-l-propen-Z- yl phosphate was dissolved in milliliters of methylene yield 26 grams of dimethyl 2-(alpha-methylbenzyloxycarbonyl)-l-methyl-l,Z-dibromoethyl phosphate as a viscous yellow liquid. Infrared spectrum analysis and elemental analysis confirmed the identity of the prodduct.

In a similar manner, in some cases employing ultraviolet light to promote the addition of the bromide, others of the fungicides of this invention are prepared from these unsaturated ester precursors, as follows:

Unsaturated ester reactant Product fungicide 5. 2-(Z-benzoyloxyethoxycarbonyl)-1- methylvinyl dimethyl phosphate (boiling point: 150 C. at 0.001 millimeter mercury pressure). Viscous liquid.

6. Dimethyl l-methyl-Z-(p-tolyloxycarbcnyl) vinyl phosphate (boiling point 115118 C. at 0.0005 millimeter mercury pressure). Flourescent yellow.

7. Phenethyl 3-(dimethoxyphosphinyloxy)- crotonate (boiling point; 140145 C. at 0.0005 millimeter mercury pressure). Pale yellow with greenish fluorescence.

8. Ethyl 3-(dicthoxyphosphinyloxy)-crotonate. 9. Diethyl l-ethoxy-2-earbethoxy-2-chlcrovinyl phosphate.

10. Beta-ehloro-beta-carbethoxy-alphamethylvinyl diethyl phosphate (boiling point: 123-126" C. at 0.15 millimeter mercury pressure).

11. Benzyl 3 (methoxyphenoxyphosphinyloxy)crotcnate (boiling point: 155 O. at 0.0005 millimeter mercury pressure).

12. Methyl 3-(methoxyphenoxy)phosphinyloxy) erotonate (boiling point: 136- 139 C. at 0.02 millimeter mercury pressure).

13. 2-ehloro-2-(methoxycarbonyl)-1-methylvinyl dimethyl phosphate (boiling point: 114-116" C. at 0.05 millimeter mercury pressure). Pale yellow liquid.

2-(2-benzoyloxyethoxycarbonyl)-1- methyl-lflrdibromoethyl dimethyl phosphate.

Dirnethyl 1-methyl-2-(p-tolyloxycarbonyl) -l,?rdibromoethy1 phosphate.

Pheuethyl 3-(dimethoxyphosphinyloxy) 3-methyl-2,Zi-dibromopropionate.

Ethyl 3-(diethoxyphosphinyloxy)-3- methyl-2, 3-dibromopropionate.

Diethyl 1-ethoxy-2-carbethoxy-Z-chloro- 1,2-dibromoethyl phosphate.

Diethyl beta-earboethoxy-beta-chloroalpha-methyl-alpha-beta dibromoethyl phosphate.

Benzyl 3-(methoxyphenoxyphosphinyloxy)-3-methyl-2,3-dibromopropionatc.

Methyl 3-(methoxyphenoxyphosphinyloxy)-3-methyl-2,3-dibromopropionate.

2,3-dibromo-2-chloro-2-(methoxycarbonyl)- l-methylethyl dimethyl phosphate (Refractive index: 1.4870 at 25 0. density: 1.67 at 25 0.). Brown liquid.

(2) In a similar manner 34 grams of benzyl 3-(dimethoxyphosphinyloxy)crotonate was brominated with 18.2 grams of bromine to give a 92% yield of benzyl 2,3 dibromo 3 (dimethoxyphosphinyloxy)butyrate, stripped at 4045 C. at 0.5 millimeter mercury pressure.

(3) 25 grams of phenyl 3-(dimethoxyphosphinyloxy) crotonate was dissolved in 50 milliliters of methylene dichloride. The solution was stirred and maintained at about C. (i2 C.) while 14 grams of bromine was added over a period of one-half hour. After all the bromine had been added, the mixture was stirred for an additional 15 minutes at about 0 C. and then was allowed to come to room temperature (about one-half hour was required). The mixture then was allowed to stand at room temperature for about 65 hours. The mixture then was stripped for three hours at 25 C. and millimeters mercury pressure. Infrared spectrum analysis of the product indicated the presence of some double bonds. The product (37 grams) then was dissolved in 50 milliliters of methylene dichloride and mixed with 0.5 milliliter of bromine at 20 C. The mixture was stripped at 20 C. and 30 millimeters mercury pressure for one hour, then at 30-35 C. and 0.5 millimeter mercury pressure for one-half hour. A 92% yield of phenyl 2,3-dibromo 3 (dimethoxyphosphinyloxy)hutyrate was obtained. The identity of the product was confirmed by elemental analysis and infrared spectrum analysis.

(4) To 20 grams of dimethyl 2-(alpha-methylbenzyloxycarbonyl)-1-methylvinyl phosphate in 30 milliliters of methylene chloride in the presence of ultraviolet light Was added with stirring 10.2 grams of bromine in 10 milliliters of methylene chloride over a period of ten minutes. The temperature of the reaction mixture was maintained from 30-35" C. The stirred mixture was held at this temperature for an additional 30 minutes. An infrared spectrum analysis indicated that substantially none of the unsaturated starting material remained. The mixture was stripped under asperator vacuum and then at 0.01 millimeter mercury pressure at 50 C. to

The fungicidal properties of this class of brominated esters were determined by the testing of typical species of those esters as follows:

Sugar beet seeds were planted about one-half inch deep in moist sandy loam soil in a series of containers, the soil being contaminated with the fungus, Pythium ultimum, as well as other damping-off fungi. Emulsions of the compound to be tested in water, each emulsion containing a different concentration of the test compound, were applied to the surface of the planted soil in the various containers, the amount of emulsion applied to the soil in each container being the same, and sufficient to disseminate the test compound in the soil surrounding the seeds. Readings were made five and ten days after the treatment to determine control of the fungi. Tested in this manner, it was found that methyl 2,3 dibromo 3-(dimethoxyphosphinyloxy)butyrate providcd substantially complete control of the fungi at a concentration of parts by weight per million parts by weight of the soil surrounding the seeds. The butyrate was not phytotoxic even at a concentration of 1000 parts by weight per million parts by weight of the soil. It was further found that phenyl 2,3-dibromo-3-(dimethoxyphosphinyloxy)butyrate and benzyl 2,3-dibromo-3-(dimethoxyphosphinyloxy)butyrate also provided substantially complete control of the fungus at a concentration of 100 parts by weight per million parts by weight of the soil and neither was phytotoxic at that dosage.

In further tests, the test compounds were formulated as coarse dusts, each dust containing a different concentration of a test compound and the dusts were thoroughly mixed with well-screened sandy loam field soil contaminated by root rot fungi, principally T hielaviopsis and Rhizoctonia solani. The treated soil then was placed in containers. Seeds of cotton, peas, sugar beets and beans then were planted in the soil. Readings were made 10 and 21 days after plan-ting to determine the extent of control of the fungi. It was found that methyl 2,3-dibromo-3-(dimethoxyphosphinyloxy)butyrate at a concentration of somewhat less than 200 parts per million (by Weight based on the soil surrounding the acids), phenyl 2,3 dibromo-3-(dimethoxyphosphinyloxy)butyrate at a concentration of 100 parts per million and benzyl 2,3- dibromo-3-(dimethoxyphosphinyloxy)butyrate at a concentration of 100 parts per million, provided substantially complete control of the fungi and that none was phytotoxic at those dosages.

In still further tests, the procedure immediately above was repeated, except that the soil was taken from the field, and the treated soil was returned to that point in the field from which the untreated soil was taken. The test crop was peas. The crop was watered and handled in normal field fashion. Readings were made three to four weeks after planting to determine control of root rot. It was found that methyl 2,3-dibromo-3-(dimethoxyphosphinyloxy)butyrate at a concentration of 50 parts per million (by weight based on the soil surrounding the seeds) and benzyl 2,3-(dimethoxyphosphinyloxy) butyrate at a concentration of 100 parts per million effected substantially complete control of the fungi without phytotoxicity.

Since these brominated esters generally are not phytotoxic at fungicidally effective concentrations, they may be used for the protection of living plants against the ravages of fungi. They are particularly effective against soil-borne fungi, although they are also effective against those which do not inhabit soil.

To destroy fungi, it is necessary to bring the fungicide into contact therewith. Since these brominated esters are not volatile at ordinary temperatures, they are most effectively brought into contact with the fungi by the application or sprays, dusts or other formulations containing the ester or esters to surfaces of objects to be protected against attack by fungi.

As shown by the tests already set out herein, these fungicides conveniently may be applied as a suspension, dispersion or emulsion in water. Alternatively, the fungicide can be formulated as a solution or suspension in a suitable nonphytotoxic organic solvent, as a dispersion or emulsion in a non-solvent therefor, as an emulsion or a solution thereof in a suitable solvent emulsified with a second, inhomogeneous liquid, or as a solid comprising the fungicide sorbed on a sorptive solid carrier. Where a light hydrocarbon oil is to be used as carrier, suitable materials for the purpose include any of the spray oils marketed commercially for this purpose. The highly aromatic hydrocarbons are preferred.

Although the solvent usually will be of mineral origin, oils of animal or of vegetable origin also may be employed in or as the carrier. In appropriate cases oxygenated solvents, such as alcohols, e.g., methanol, ethanol, isopropyl alcohol, n-butyl alcohol .and amyl alcohol, ketones, e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, etc., glycols and glycol ethers and chlorinated solvents may be employed in or as the carrier.

Solutions of the fungicides may be applied as such, or they may be suspended in water and the suspension or emulsion applied. Thus, a relatively concentrated solution of the fungicide in a water-immiscible solvent may be prepared, with added emulsifying, dispersing or other surface-active agents, and the concentrate diluted with water to form a uniform fine emulsion for application.

Minor amounts, for example, about 0.5% by weight to about by weight, of emulsifying agents may be included to promote dispersion of the fungicide in the carrier. Suitable emulsifying agents include, among others, alkaryl sulfonates, sulfates of long-chain fatty acids, alkylaryl polyoxyethylene glycol ethers, sulfonated white oils, sorbitan esters of long-chain fatty acids, alkylamide sulfona-tes and the like. Although both anionand cation-active wetting and emulsifying agents may be used for this purpose, the non-ionic agents are preferred since the concentrates in which they are present have increased stability and do not suffer phase separation when diluted with hard water. Suitable non-ionic agents which may be used are available commercially as, for example, Triton X- and Lissapol N-believed to be condensation products of alkylphenols with ethylene oxide-and Tweensbelieved to be condensation products of ethylene oxide and higher fatty acid esters, for example, oleic acid ester of anhydrosorbitols.

Liquid compositions of the fungicides suitable for application contain the fungicide in concentrations generally with-in the range of from about 0.01% by weight to about 25% by weight.

The fungicide may be absorbed or adsorbed in or on a sorptive carrier, such as finely divided clay, talc, gypsum, lime, wood flour, fullers earth, kieselguhr, or the like. The solid composition, or dust, may contain from as little as 1% by weight of the fungicide to 50% by weight of the fungicide, or even more. It may be prepared as a dust, or as granules designed to be worked into soil. Compositions formulated as wettable powders are particularly suitable. Wettable powders can be prepared suitable for suspension in water with or without the aid of conventional dispersing or defiocculating agents and with or Without such adjuvants as oils, stickers, wetting agents, etc.

For field application to soil, the rate of application of these fungicides may be varied from about 0.5 to 100 or more pounds per acre. It will be appreciated that the rate of application is subject to variation according to the fungi involved, the particular fungicide or fungicides used, the particular species of plants involved, and the local conditions, for example, temperature, humidity, moisture content of the soil, nature of the soil, and the like. Effective resolution of these factors is well within the skill of those well versed in the fungicide art. The fungicidal composition can, depending upon its character, be sprayed or dusted upon the surfaces to be protected from fungi, or in the case of application to soils, it can be applied by flooding, by addition to irrigation water, by mixing with the soil, by injection into the soil, or by combination of these techniques.

One or more of the new fungicides may be the sole biologically active material, or there may be present one or more materials. Thus, when applied to soils, the new fungicides may be accompanied by soil conditioners, fertilizers, nematicides, or other soil amenders. When applied to plants, there may be included insecticides, plant growth-modifying agents or the like. When used for nonagricultural purposes, other materials may be present. Thus, the fungicide may be included in pastes used in book bindings to prevent mildew and rot, or it may be included with other preservatives such as copper salts, in compositions used for protecting sills and pilings. It is thus apparent that these new fungicides can be used in any application where a non-phytotoxic fungicide is required.

Since they are not generally phytotoxic at fungicidally active concentrations, these new fungicides may be applied to the soil at the same time as crop seeds are planted, or they may be applied to soil in Which the crop is growing. Of course, they may be applied before the crop is planted, for example, when the soil is being tilled.

In addition to being toxic toward Thielaviopsis, Rhizoctonia and Pythium fungi, these fungicides also are toxic toward such fungi as the Fusarium fungi, Verticillium fungi, and the like.

We claim as our invention:

1. Compounds of the formula:

wherein R is hydrocarbon containing up to 10 carbon atoms of the group consisting of alkyl, aryl and aralkyl; R is a member of the group consisting of hydrogen and alkyl groups of up to 10 carbon atoms; R is a member of the group consisting of hydrogen, chlorine, bromine and alkyl of up to 10 carbon atoms, and R contains up to 10 carbon atoms and is a member of the group consisting of aryl and aralkyl.

2. Compounds of the formula:

wherein each alkyl contains 1 to 4 carbon atoms and R contains up to 10 carbon atoms and is a member of the group consisting of aryl and araikyl.

3. Compounds of the formula:

Br Br UNITED STATES PATENTS 3,005,841 10/1961 Silverman 260461 3,081,220 3/1963 Turner et a1 2604 61 3,093,536 6/1963 Loeflier 260'461 FOREIGN PATENTS 784,986 10/1957 Great Britain.

CHARLES B. PARKER, Primary Examiner.

FRANK M. SIKORA, Assistant Examiner. 

1. COMPOUNDS OF THE FORMULA: 